From Dog

Pyrexia is a technical term for fever, which in dogs is defined as a rise in core body temperature > 39.5 0C.

Fever can be differentiated from hyperthermia ('heat stroke') by the circumstances surrounding it and its response to anti-pyretic medications.

The causes of pyrexia are manifold, from chronic inflammatory states to infections but the common initiating chemical is what is collectively termed a 'pyrogens' - literally any molecule which can induce fever.

Pyrogens are present in the blood and evoke systemic changes in body core temperatures through induction of endogenous immunoregulatory proteins called cytokines are released from areas of infection or damage and evoke elevated body metabolic rate, shivering, sweating, etc.

Peripheral cytokines can pass the blood-brain barrier by active and saturable transport systems which are specific for individual cytokines and the role of the CNS is critical for this response as hypothalamic modulation of core temperature is regulated by both humoral and neuronal mechanisms[1].

Depending on the route by which pyrogens gain access to the brain, they stimulate a variety of cytokines including tumor necrosis factor alpha (TNF-a), which is the first cytokine which appears in the circulation[2], followed by traces of interleukin-1ß (IL-1ß[3] and high amounts of IL-6[4], IL-8[5] as well as other cytokines such as macrophage inflammatory protein-1[6].

A similar cytokine cascade can be monitored in response to other pyrogenic compounds of Gram-positive and Gram-negative bacteria such as superantigens, peptidoglycans or muramyl-dipeptides. Invading viruses or synthetic viral compounds activate a distinct pattern of cytokine production including interferons as initial mediators within the cytokine cascade


  1. Banks WA & Kastin A (1991) Blood to brain transport of interleukin links the immune and central nervous systems. Life Sciences 48:L117-L121
  2. Kluger MJ (1991) Fever: role of pyrogens and cryogens. Physiological Reviews 71:93-127
  3. Jansky L et al (1995) Production of systemic and hypothalamic cytokines during the early phase of the endotoxin fever. Neuroendocrinology 62:55-61
  4. Roth J et al (1993) Kinetics of systemic and intrahypothalamic IL-6 and tumor necrosis factor during endotoxin fever in the guinea pig. American Journal of Physiology 265:R653-R658
  5. Van Zee KJ et al (1991) IL-8 in septic shock, endotoxemia, and after IL-1 administration. Journal of Immunology 146:3478-3482
  6. Ziegler SF et al (1991) Induction of macrophage inflammatory protein-1 gene expression in human monocytes by lipopolysaccharide and IL-7. Journal of Immunology 147:2234-2239